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Integrin-facilitated transcytosis for enhanced penetration of advanced gliomas by poly(trimethylene carbonate)-based nanoparticles encapsulating paclitaxel

Paper ID Volume ID Publish Year Pages File Format Full-Text
6262 471 2013 11 PDF Available
Title
Integrin-facilitated transcytosis for enhanced penetration of advanced gliomas by poly(trimethylene carbonate)-based nanoparticles encapsulating paclitaxel
Abstract

The treatment of cerebral tumor, especially advanced gliomas, represents one of the most formidable challenges in oncology. In this study, integrin-mediated poly(trimethylene carbonate)-based nanoparticulate system (c(RGDyK)–NP) was proposed as a delivery vehicle for enhancing drug penetration and chemotherapy of malignant gliomas. Following the recognition by integrin proteins on cell surface, c(RGDyK)–NP could be energy-dependently internalized by human U87MG glioma cells through a multiple endocytic pathway. The tumor penetration, homing specificity and anticancer efficacy of PTX-loaded c(RGDyK)–NP (c(RGDyK)–NP/PTX) were performed on the 3D glioma spheroids, the U87MG glioma cells and the intracranial glioma mice model, respectively. Compared with conventional nanoparticles (NP/PTX) and Taxol, c(RGDyK)–NP/PTX showed the strongest penetration and accumulation into 3D glioma spheroids, an obvious microtubule stabilization effect to U87MG glioma cells, a significant homing specificity to malignant glioma in vivo, and an extended median survival time in the intracranial glioma-bearing mice. Furthermore, preliminary in vivo subacute toxicity was also evaluated by measuring the histopathology, blood cell counts and clinical biochemistry parameters, and the results revealed no obvious subacute toxicity to hematological system, major organs or tissues were observed post successive intravenous injection of c(RGDyK)–NP. Therefore, our results suggested that cyclic RGD-conjugated PEG–PTMC nanoparticle could be a promising vehicle for enhancing the penetration and cxhemotherapy of high-grade malignant gliomas.

Keywords
Advanced gliomas; PEG–PTMC; Endocytic mechanism; Glioma spheroids; Glioma penetration; Anti-glioma efficacy; In vivo toxicity
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Integrin-facilitated transcytosis for enhanced penetration of advanced gliomas by poly(trimethylene carbonate)-based nanoparticles encapsulating paclitaxel
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 12, April 2013, Pages 2969–2979
Authors
, , , , , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us